Document Type

Thesis

Date of Award

Fall 1-31-2016

Degree Name

Master of Science in Pharmaceutical Engineering - (M.S.)

Department

Chemical, Biological and Pharmaceutical Engineering

First Advisor

Piero M. Armenante

Second Advisor

Norman W. Loney

Third Advisor

Laurent Simon

Abstract

In most industrial applications, stirred tanks and reactors are typically provided with baffles to improve their mixing characteristics. However, in a number of pharmaceutical production facilities unbaffled vessels are commonly used. The absence of baffles is preferred in such cases because it reduces the potential for contamination and makes cleaning the vessel between batches easier. However, the lack of baffles also has a negative impact on the system’s hydrodynamics since it often results in poor mixing of the batch, especially if the impeller is centrally placed, since the liquid in such a system is subject to a strong tangential flow, but low axial and radial flows. This hydrodynamic regime is highly undesirable if effective top-to-bottom liquid recirculation is required, and especially if a second phase (e.g., solid particles, immiscible liquids) must be dispersed and incorporated into the liquid bulk. For this reason, impellers in unbaffled pharmaceutical vessels are typically placed off-center, and, additionally, they may be mounted on a shaft that is angled with respect to the vessel vertical centerline. This lack of symmetry introduces some degree of “baffling” effects, in that it promotes stronger vertical recirculation of the liquid, and improves the suspension of settling solids and the incorporation of floating solids.

Despite their industrial relevance, especially for the pharmaceutical industry, extremely limited information is available on the hydrodynamics of vessels provided with angle-mounted impellers. Therefore, in this work, experimental and computational tools were used to determine the hydrodynamics of fluids in a Plexiglas, custom-made, scaled-down version (diameter: 316 mm) of an industrial vessel with an elliptical bottom and provided with two angle-mounted (by 5° off the vertical) A-310 Lightnin impellers. The system was operated under different operating conditions in order to replicate the mixing characteristics of the industrial system. Computational Fluid Dynamics (CFD) was used to quantify the hydrodynamics of this system under different geometric configurations (such as liquid level), agitation speeds, and for different fluid rheologies. In all cases a multiple reference frame (MRF) computational approach was used and turbulence was modeled using the k-ε method. In addition, Particle Image Velocimetry (PIV) was used to experimentally determine the velocity flow field in water for some of these configurations in order to validate the CFD predictions, thus providing guidance on the optimal operation of these industrial system.

The results obtained here indicate that there is substantial agreement between the CFD predictions and the PIV experimental results. The flow in the vessel appears to be very complex. The axial pumping action of the impellers produces a downward flow impinging the bottom of the vessel resulting in flow splitting and in the formation of a less well-mixed zone near the vessel bottom that persists even when the impeller velocity is substantially increased. This zone could be the preferential location for the sedimentation of settling solids in the liquid.

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